Abstract
Simple SummaryThis study was conducted to demonstrate how a vitrified embryo transfer procedure incurs phenotypic and molecular changes throughout life. This study reports the first evidence describing that embryonic manipulation during a vitrified embryo transfer cycle induced molecular modifications, concerning oxidative phosphorylation and dysregulations in zinc and lipid metabolism in liver tissue, which has been reported as responsible for postnatal variations of the phenotype.Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo.
Highlights
Since their implementation, assisted reproductive technologies (ARTs) have made major contributions to human health, livestock production and environmental management in the past and will continue to do so in future [1,2]
From the outset there has been concern about the influence of these technologies in embryo and postnatal development. This is the basis of the Developmental Origins of Health and Disease (DOHaD) theory, which posits that environmental stresses during development can increase the risk of disease later in life [3]
Several evidences of long-lasting ART consequences have been reported in properly designed animal models [3,7,8,9,14,15,16], the vast majority of these results has been evidenced in the mouse model
Summary
Since their implementation, assisted reproductive technologies (ARTs) have made major contributions to human health, livestock production and environmental management in the past and will continue to do so in future [1,2]. In response to environmental signals, this developmental plasticity allows phenotypic changes in developing embryos to be better suited to the environment in which they will be born Extreme stressors, such as ART conditions, can force developing embryos to carry out a strong reshaping of their developmental trajectories to guarantee their short-term survival [3,4,5]. This reprogramming in embryonic cells that subsequently forms tissues and organ systems may influence an individual’s susceptibility to alterations in growth, development and health [3,6,7,8,9,10,11,12,13]. Many molecular/physiological events during human embryo development are more similar to those in rabbits than in mice, placing the rabbit as a pertinent animal model choice to study the impact of a disturbed periconceptional environment during ART and obtain results that are feasibly transferable to the clinic
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